Plants can be Useful for Studying Variable Drug Responses in Humans

While prescription medications work successfully to cure an ailment in some people, in others the same dose of the same drug can cause an adverse reaction or no response at all.

According to a research team led by Sean Cutler, an assistant professor of plant cell biology at UC Riverside, such variation in drug responses can be analyzed by studying much simpler organisms – like plants.

Focusing on Arabidopsis thaliana, a weedy plant in the mustard family, Cutler’s lab discovered a key protein in the plant that creates drug resistance. Called UGT (UDP-glycosyltransferase), the protein is a member of a family of proteins that also affect drug sensitivity in humans.

In their research, Cutler and his research team first screened and tested thousands of drug-like compounds in the lab as they searched for new inhibitors of plant growth. In the process, they discovered a new molecule, called hypostatin, which acts like a drug in inhibiting plant growth in some Arabidopsis plants. At the same time, the researchers grew Arabidopsis plants in a solution containing hypostatin, which allowed the plant cells to take up hypostatin.

Cutler and his team found that the plants’ UGT activates hypostatin by adding a sugar molecule to it. They also found that in plants that had a genetically defective UGT, hypostatin did not work properly because no sugar molecules – necessary for activating hypostatin – were added to it; in such plants, therefore, growth was not affected.

“This mechanism is very similar to that seen in humans, where altered drug sensitivity can occur because of defective or atypical sugar-tagging proteins,” Cutler said.